This project contains three related parts: (1) The major portion is directed toward elucidation of the structural, thermodynamic, and kinetic and assembly properties of the gelation of sickle cell hemoglobin with the two ultimate aims: (a) To obtain conditions and/or agents useful for clinical inhibition of gelation and sickling; (b) To characterize in a specific system phenomena which occur in a number of important systems: nucleation, helical fiber formation and growth, phase condensation, phase separation and nematic liquid crystal formation, and possible dense fibrous alignment; or, from another point of view, highly cooperative processes in extended allosteric systems. Methodological approach includes kinetic, equilibrium and structural studies by ultracentrifugation, light scattering, viscosity and other physical-chemical techniques, and by electron microscopy. (2) The second part concerns the use of the property of gelation of hemoglobin S as marker for quaternary structure and the critical allosteric R-T transition in hemoglobin, and thus the use of hemoglobin S in the study of structure-function relations in hemoglobin in general. (3) The third part concerns equilibrium, kinetic and structural studies on normal hemoglobin which bear on specific aspects of the mechanisms of allosteric ligand binding by hemoglobin.